Physiological Background of Differences in Quantitative Diffusion-Weighted Magnetic Resonance Imaging Between Acute Malignant and Benign Vertebral Body Fractures: Correlation of Apparent Diffusion Coefficient With Quantitative Perfusion Magnetic Resonance Imaging Using the 2-Compartment Exchange Model.

OBJECTIVE: To test the hypothesis that apparent diffusion coefficient (ADC) in vertebral bone marrow of benign and malignant fractures is related to the volume of the interstitial space, determined with dynamic contrast-enhanced (DCE) magnetic resonance imaging. METHODS: Patients with acute benign (n = 24) and malignant (n = 19) vertebral body fractures were examined at 1.5 T. A diffusion-weighted single-shot turbo-spin-echo sequence (b = 100 to 600 s/mm) and DCE turbo-FLASH sequence were evaluated. Regions of interest were manually selected for each fracture. Apparent diffusion coefficient was determined with a monoexponential decay model. The DCE magnetic resonance imaging concentration-time curves were analyzed using a 2-compartment tracer-kinetic model. RESULTS: Apparent diffusion coefficient showed a significant positive correlation with interstitial volume in the whole study population (Pearson r = 0.66, P < 0.001), as well as in the malignant (Pearson r = 0.64, P = 0.004) and benign (Pearson r = 0.52, P = 0.01) subgroup. A significant correlation between ADC and the permeability-surface area product could be observed when analyzing the whole study population (Spearman rs = 0.40, P = 0.008), but not when separately examining the subgroups. Plasma flow showed a significant correlation with ADC in benign fractures (Pearson r = 0.23, P = 0.03). Plasma volume did not show significant correlations with ADC. CONCLUSIONS: The results support the hypothesis that the ADC of a lesion is inversely correlated to its cellularity. This explains previous observations that ADC is reduced in more malignant lesions.

Tumor load in patients with multiple myeloma: ß2-microglobulin levels versus whole-body MRI.

OBJECTIVE: Beta-2-microglobulin is a serum maker of tumor burden in hematologic malignancies. We aimed to correlate serum ß2-microglobulin levels in patients with multiple myeloma (MM) to tumor mass determined by whole-body MRI. MATERIALS AND METHODS: We retrospectively included patients with newly diagnosed, untreated MM who underwent whole-body MRI at our institution between 2003 and 2011. Patients with a glomerular filtration rate of less than 60 mL/min were excluded from analysis because ß2-microglobulin levels are increased in renal failure. Thirty patients could be included. Whole-body MRI examinations (T1-weighted turbo spin-echo and STIR sequences) were assessed by two musculoskeletal radiologists in consensus for focal lesions and the presence of diffuse myeloma infiltration. The presence of diffuse infiltration was confirmed by histology as the reference standard. MM was staged according to the Durie and Salmon PLUS staging system. RESULTS: According to whole-body MRI findings, MM was classified as Durie and Salmon PLUS stage I (low grade) in 13 patients, stage II (intermediate grade) in six patients, and stage III (high grade) in 11 patients. As we expected, most patients with stage I disease (12/13) had normal ß2-microglobulin levels (≤ 3 mg/L). Higher ß2-microglobulin values were associated with a higher stage of disease (p < 0.05). However, five of six patients with stage II MM and five of 11 patients with stage III MM showed normal ß2-microglobulin levels. Thus, 10 of 17 patients (58.8%) with substantial infiltration in the bone marrow showed false-negative ß2-microglobulin levels. CONCLUSION: Serum ß2-microglobulin levels correlate with tumor stage in MM. However, it may be misleading as a marker of tumor load in a subset of patients with substantial myeloma infiltration in the bone marrow. Whole-body MRI may display the full tumor load and correctly show the extension of myeloma infiltrates.

Quantitative evaluation of benign and malignant vertebral fractures with diffusion-weighted MRI: what is the optimum combination of b values for ADC-based lesion differentiation with the single-shot turbo spin-echo sequence?

OBJECTIVE: The purpose of our study was to determine the optimum combination of b values for calculating the apparent diffusion coefficient (ADC) using a diffusion-weighted (DW) single-shot turbo spin-echo (TSE) sequence in the differentiation between acute benign and malignant vertebral body fractures. SUBJECTS AND METHODS: Twenty-six patients with osteoporotic (mean age, 69 years; range, 31.5-86.2 years) and 20 patients with malignant vertebral fractures (mean age, 63.4 years; range, 24.7-86.4 years) were studied. T1-weighted, STIR, and T2-weighted sequences were acquired at 1.5 T. A DW single-shot TSE sequence at different b values (100, 250, 400, and 600 s/mm(2)) was applied. On the DW images for each evaluated fracture, an ROI was manually adapted to the area of hyperintense signal intensity on STIR-hypointense signal on T1-weighted images. For each ROI, nine different combinations of two, three, and four b values were used to calculate the ADC using a least-squares algorithm. The Student t test and Mann-Whitney U test were used to determine significant differences between benign and malignant fractures. An ROC analysis and the Youden index were used to determine cutoff values for assessment of the highest sensitivity and specificity for the different ADC values. The positive (PPV) and negative predictive values (NPV) were also determined. RESULTS: All calculated ADCs (except the combination of b = 400 s/mm(2) and b = 600 s/mm(2)) showed statistically significant differences between benign and malignant vertebral body fractures, with benign fractures having higher ADCs than malignant ones. The use of higher b values resulted in lower ADCs than those calculated with low b values. The highest AUC (0.85) showed the ADCs calculated with b = 100 and 400 s/mm(2), and the second highest AUC (0.829) showed the ADCs calculated with b = 100, 250, and 400 s/mm(2). The Youden index with equal weight given to sensitivity and specificity suggests use of an ADC calculated with b = 100, 250, and 400 s/mm(2) (cutoff ADC, < 1.7 × 10(-3) mm(2)/s) to best diagnose malignancy (sensitivity, 85%; specificity, 84.6%; PPV, 81.0%; NPV, 88.0%). CONCLUSION: ADCs calculated with a combination of low to intermediate b values (b = 100, 250, and 400 s/mm(2)) provide the best diagnostic performance of a DW single-shot TSE sequence to differentiate acute benign and malignant vertebral body fractures.

Neuroendocrine tumor recurrence: diagnosis with 68Ga-DOTATATE PET/CT.

PURPOSE: To evaluate diagnostic performance of gallium 68-tetraazacyclododecane tetraacetic acid-octreotate ((68)Ga-DOTATATE) in detection of recurrent neuroendocrine tumors (NETs). MATERIALS AND METHODS: Approval was waived by the local ethics committee for this retrospective study. Between 2007 and 2011, 63 patients (mean age, 58 years) were examined with (68)Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) after primary NET curative resection. Reasons for PET/CT were regular follow-up examinations (n = 30), increased plasma levels of tumor markers (n = 27), or clinical suspicion of recurrence (n = 6). Final diagnosis was determined with histopathologic verification (n = 25) or clinical follow-up (n = 38). PET/CT scans were evaluated in consensus by two readers without blinding to clinical information and independently by two readers with blinding. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Final diagnosis of NET recurrence was determined in 29 patients. In three other patients, tumors of nonneuroendocrine origin were diagnosed. (68)Ga-DOTATATE PET/CT helped identify NET recurrence in 26 of 29 patients (sensitivity, 90%) and exclude presence of recurrent NET in 28 of 34 patients (specificity, 82% ). PET/CT provided false-positive and false-negative results in six and three patients (PPV, 81% [26 of 32]; NPV, 90% [28 of 31]; accuracy, 86% [54 of 63]). In gastroenteropancreatic NET (n = 45), sensitivity was 94% (17 of 18); specificity was 89% (24 of 27); PPV was 85% (17 of 20); NPV was 96% (24 of 25); and accuracy was 91% (41 of 45). Two blinded readers achieved sensitivity of 79% (23 of 29) and 76% (22 of 29); specificity of 85% (29 of 34) and 94% (32 of 34) (κ = 0.80); and accuracy of 83% and 86%. CONCLUSION: (68)Ga-DOTATATE PET/CT is accurate in detection of recurrent NET. Blinded PET/CT review markedly decreased sensitivity, underlining importance of considering clinical parameters in NET recurrence. Present results must be further validated to substantiate use of (68)Ga-DOTATATE PET/CT in routine follow-up after curative resection of NET.

Quantitative analysis of acute benign and malignant vertebral body fractures using dynamic contrast-enhanced MRI.

OBJECTIVE: The objective of our study was to evaluate quantitative dynamic contrast-enhanced MRI (DCE-MRI) based on tracer kinetic modeling of perfusion in the differentiation of benign from malignant vertebral fractures. SUBJECTS AND METHODS: Patients with 26 osteoporotic vertebral fractures (18 women, eight men; mean age, 69 years) and patients with 20 malignant vertebral fractures (nine women, 11 men; mean age, 63.4 years) underwent dynamic contrast-enhanced MRI. T1-weighted, STIR, and T2-weighted sequences were acquired at 1.5 T. Dynamic contrast-enhanced image sets were acquired with a 2D saturation-recovery spoiled gradient-echo sequence. Regions of interest in parameter maps of mean transit time (MTT) and plasma flow in the fractured vertebral bodies were analyzed with a two-compartment tracer kinetic model. Plasma flow, plasma volume (PV), extraction flow, and interstitial volume were calculated. The forward volume transfer constant (K(trans)) and the extracellular volume (ECV) were derived. A two-tailed Fisher exact test, Mann-Whitney U test, and receiver operating characteristic analysis were performed. RESULTS: Forty-four vertebral fractures in 44 patients could be evaluated. In spots of increased plasma flow, interstitial volume (p = 0.0003), ECV (p = 0.002), and extraction flow (p = 0.03) for osteoporotic and malignant vertebral fractures were significantly different. The mean interstitial volume was 28.62 mL/100 mL for osteoporotic fractures and 11.73 mL/100 mL for malignant fractures, and the area under the curve (AUC) was 0.819 for a cutoff of 11.72 mL/100 mL or less indicating malignancy (sensitivity, 63.2%; specificity, 96.0%). The mean ECV was 52.68 mL/100 mL for osteoporotic fractures and 36.71 mL/100 mL for malignant fractures, and the AUC was 0.802 for a cutoff of 35.83 mL/100 mL or less indicating malignancy (sensitivity, 63.2%; specificity, 92.0%). The mean extraction flow was 15.19 mL/100 mL/min for osteoporotic fractures and 23.67 mL/100 mL/min for malignant fractures, and the AUC was 0.693 for a cutoff of 6.52 mL/100 mL/min or less indicating malignancy (sensitivity, 57.9%; specificity, 92.0%). K(trans), plasma flow, and PV in the spots of increased plasma flow and all quantitative perfusion parameters in the regions of increased MTT did not show any significant differences between benign and malignant fractures. CONCLUSION: In spots of high plasma flow, which can be determined with a deconvolution analysis, the quantitative perfusion parameters of interstitial volume, ECV, and extraction flow are significantly different between acute osteoporotic and malignant vertebral fractures and can aid in the distinction between the two entities.

Comparison of qualitative and quantitative evaluation of diffusion-weighted MRI and chemical-shift imaging in the differentiation of benign and malignant vertebral body fractures.

OBJECTIVE: The objective of our study was to compare the diagnostic value of qualitative diffusion-weighted imaging (DWI), quantitative DWI, and chemical-shift imaging in a single prospective cohort of patients with acute osteoporotic and malignant vertebral fractures. SUBJECTS AND METHODS: The study group was composed of patients with 26 osteoporotic vertebral fractures (18 women, eight men; mean age, 69 years; age range, 31 years 6 months to 86 years 2 months) and 20 malignant vertebral fractures (nine women, 11 men; mean age, 63.4 years; age range, 24 years 8 months to 86 years 4 months). T1-weighted, STIR, and T2-weighted sequences were acquired at 1.5 T. A DW reverse fast imaging with steady-state free precession (PSIF) sequence at different delta values was evaluated qualitatively. A DW echo-planar imaging (EPI) sequence and a DW single-shot turbo spin-echo (TSE) sequence at different b values were evaluated qualitatively and quantitatively using the apparent diffusion coefficient. Opposed-phase sequences were used to assess signal intensity qualitatively. The signal loss between in- and opposed-phase images was determined quantitatively. Two-tailed Fisher exact test, Mann-Whitney test, and receiver operating characteristic analysis were performed. Sensitivities, specificities, and accuracies were determined. RESULTS: Qualitative DW-PSIF imaging (delta = 3 ms) showed the best performance for distinguishing between benign and malignant fractures (sensitivity, 100%; specificity, 88.5%; accuracy, 93.5%). Qualitative DW-EPI (b = 50 s/mm(2) [p = 1.00]; b = 250 s/mm(2) [p = 0.50]) and DW single-shot TSE imaging (b = 100 s/mm(2) [p = 1.00]; b = 250 s/mm(2) [p = 0.18]; b = 400 s/mm(2) [p = 0.18]; b = 600 s/mm(2) [p = 0.39]) did not indicate significant differences between benign and malignant fractures. DW-EPI using a b value of 500 s/mm(2) (p = 0.01) indicated significant differences between benign and malignant vertebral fractures. Quantitative DW-EPI (p = 0.09) and qualitative opposed-phase imaging (p = 0.06) did not exhibit significant differences, quantitative DW single-shot TSE imaging (p = 0.002) and quantitative chemical-shift imaging (p = 0.01) showed significant differences between benign and malignant fractures. CONCLUSION: The DW-PSIF sequence (delta = 3 ms) had the highest accuracy in differentiating benign from malignant vertebral fractures. Quantitative chemical-shift imaging and quantitative DW single-shot TSE imaging had a lower accuracy than DW-PSIF imaging because of a large overlap. Qualitative assessment of opposed-phase, DW-EPI, and DW single-shot TSE sequences and quantitative assessment of the DW-EPI sequence were not suitable for distinguishing between benign and malignant vertebral fractures.

The role of 68Ga-DOTATATE PET/CT in suspected neuroendocrine tumors.

UNLABELLED: In patients with suspected but yet not localized neuroendocrine tumors (NETs), early diagnosis or reliable exclusion is crucial for optimal individual prognosis and therapy. Despite recourse to several imaging modalities, the definite diagnosis of NET can be challenging. Therefore, we tested (68)Ga-DOTATATE PET/CT as a tool for improved diagnosis in a cohort of patients with suspected, nonlocalized NET. METHODS: (68)Ga-DOTATATE PET/CT recordings were obtained in 104 consecutive patients meeting at least one of the following criteria: clinical suspicion of NET (n = 70), elevated blood levels of tumor markers (n = 49), and image-based suspicion of NET (n = 53). The presence of NET was validated by histopathology (n = 49) or clinical follow-up of 107 ± 59 wk (n = 55). RESULTS: In 36 of 104 patients (35%), NET was histologically verified, most frequently located in the small bowel (10/36), pancreas (8/36), lung (5/36), and stomach (2/36). Twelve patients had tumors of nonneuroendocrine origin, and 7 patients had benign tumors. (68)Ga-DOTATATE PET/CT identified NET in 29 of the 36 cases and excluded the presence of a NET in 61 of the 68 non-NET patients, indicating a sensitivity of 81% and specificity of 90%. The PET/CT gave a false-positive result in 7 patients and a false-negative in another 7 patients, indicating positive and negative predictive values of 81% and 90%, respectively, and an accuracy of 87%. Chromogranin A levels were significantly higher in both PET-positive patients (1,841 vs. 342 ng/mL; P < 0.05) and patients with verified NET (2,214 vs. 524 ng/mL; P < 0.05). CONCLUSION: In patients with suspected NETs due to clinical symptoms, elevated levels of tumor markers, or indeterminate tumors suggestive of NET, (68)Ga-DOTATATE PET/CT is highly accurate, thus supporting its use in clinical routine diagnostics.

Radioembolization of symptomatic, unresectable neuroendocrine hepatic metastases using yttrium-90 microspheres.

PURPOSE: To evaluate safety, efficacy, and symptom-control of radioembolization in patients with unresectable liver metastases from neuroendocrine tumors (NETLMs). MATERIALS AND METHODS: Forty-two patients (mean age of 62 years) with treatment-refractory NETLMs underwent radioembolization using yttrium-90 ((90)Y) resin microspheres. Posttreatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST) and tumor-marker levels. Laboratory and clinical toxicities and clinical symptoms were monitored. RESULTS: The median activity delivered was 1.63 GBq (range 0.63-2.36). Imaging follow-up using RECIST at 3-month follow-up demonstrated partial response, stable disease, and progressive disease in 22.5, 75.0, and 2.5% of patients, respectively. In 97.5% of patients, the liver lesions appeared hypovascular or partially necrotic. The mean follow-up was 16.2 months with 40 patients (95.2%) remaining alive. The median decrease in tumor-marker levels at 3 months was 54.8% (chromogranin A) and 37.3% (serotonin), respectively. There were no acute or delayed toxicities greater than grade 2 according to Common Terminology Criteria for Adverse Events [CTCAE (v3.0)]. No radiation-induced liver disease was noted. Improvement of clinical symptoms 3 months after treatment was observed in 36 of 38 symptomatic patients. CONCLUSION: Radioembolization with (90)Y-microspheres is a safe and effective treatment option in patients with otherwise treatment-refractory NETLMs. Antitumoral effect is supported by good local tumor control, decreased tumor-marker levels, and improved clinical symptoms. Further investigation is warranted to define the role of radioembolization in the treatment paradigm for NETLMs.

Correlation between vacuum phenomenon on CT and fluid on MRI in degenerative disks.

OBJECTIVE: The purpose of this study is to correlate the presence of intradiscal vacuum phenomenon on CT to that of intradiscal fluid on MRI. SUBJECTS AND METHODS: In a prospective study, 20 patients with lumbar vacuum phenomenon on CT underwent two MRI examinations. One was performed after mobilization, and the other was performed after 6 hours of bed rest. T2-weighted turbo-spin echo (TSE), STIR, T1-weighted TSE, and four consecutive T2-weighted TSE sequences were performed on a 1.5-T scanner. Ninety-five discal segments were assessed for the presence of intradiscal fluid or hyperintense signal on the T2-weighted MRI examinations and were correlated with the presence of vacuum phenomenon on CT, degenerative endplate abnormalities on CT, and edema on MRI. RESULTS: Sixty-nine of 95 discal segments (72.6%) showed vacuum phenomenon on CT. Sixteen of those 69 discal segments (23.1%) showed intradiscal fluid (n = 12) or hyperintense signal (n = 4) on MRI examinations performed after mobilization. Forty-one of 69 discal segments (59.4%) with vacuum phenomenon showed intradiscal fluid (n = 29) or hyperintense signal (n = 12) on MRI examinations performed after bed rest. Seventeen segments showed only fluid after bed rest. Nine segments showed more fluid after bed rest than after mobilization. Three segments showed an unchanged amount of fluid. There was a significant correlation between the presence of intradiscal fluid and the amount of bone marrow edema on MRI and the presence of degenerative endplate abnormalities on CT, respectively. CONCLUSION: The replacement of intradiscal vacuum phenomenon by intradiscal fluid is a time- and position-dependent dynamic process and is related to Modic type 1 degenerative disk disease and degenerative endplate changes.

Treatment with octreotide does not reduce tumor uptake of (68)Ga-DOTATATE as measured by PET/CT in patients with neuroendocrine tumors.

UNLABELLED: We hypothesized that (68)Ga-DOTATATE uptake of neuroendocrine tumors is sensitive to therapy with a nonradioactive somatostatin analog. METHODS: (68)Ga-DOTATATE PET/CT was used to examine 105 patients, 35 of whom had been pretreated with long-acting octreotide. The maximum standardized uptake value (SUV(max)) of target tissues, as well as metastases, was compared between the groups of patients with (group 1) and without (group 2) octreotide treatment. RESULTS: The SUV(max) of the spleen and liver was significantly lower in group 1 than in group 2 (both P < 0.001). There were no significant group differences in SUV(max) for primary tumors (28.6 ± 6.8 vs. 32.9 ± 31.5) or metastases in the liver (27.2 ± 14.8 vs. 25.7 ± 10.7), lymph nodes (41.4 ± 19.5 vs. 25.0 ± 6.3), or skeleton (39.5 ± 22.0 vs. 15.4 ± 7.8). In 9 patients available for intraindividual comparison, tumor uptake was unaffected by treatment with somatostatin analogs (21.7 vs. 20.6; P = 0.93). CONCLUSION: Treatment with a long-acting somatostatin analog did not significantly reduce (68)Ga-DOTATATE binding in neuroendocrine tumors but tended to improve the tumor-to-background ratio.

Quantitative analysis of the diffusion-weighted steady-state free precession signal in vertebral bone marrow lesions.

OBJECTIVES: : Diffusion-weighted steady-state free precession (DW-SSFP) sequences have shown great potential for the differential diagnosis of benign osteoporotic and malignant neoplastic vertebral compression fractures, which appear hypo- to isointense or hyperintense in DW-SSFP magnetic resonance imaging, respectively. In contrast to other diffusion weighting sequences, the DW-SSFP signal depends not only on the apparent diffusion coefficient (ADC), but also on the tissue relaxation times and sequence parameters. The purpose of the present study was to provide a detailed analysis of the DW-SSFP signal in benign and malignant vertebral lesions (VLs) and in vertebral bone marrow (VBM) to understand the observed signal alterations and their dependence on tissue and sequence parameters. MATERIALS AND METHODS: : Magnetic resonance imaging was performed in 40 patients with benign (n = 20) or malignant (n = 20) VLs to determine the fat fraction and tissue parameters (ADC, T1, T2, T2*) for both the water and fat signal. With these values, the DW-SSFP signal was simulated and compared with the measured signals for different diffusion gradients by determining the signal intensity ratio between the SSFP signals of the lesions and of normal-appearing VBM for both malignant and benign VLs. RESULTS: : The simulated DW-SSFP contrast agreed well with the measured contrast and provided a very good differentiation between benign osteoporotic and malignant VLs. ADCs were significantly different in both lesion types (malignant 1.36 vs. osteoporotic 1.77 × 10 mm/s); however, the observed contrast differences were caused predominantly by an opposed-phase readout in combination with significantly different T2* values (malignant 22 vs. osteoporotic 14 ms) and fat fractions (malignant 3.9% vs. osteoporotic 12%) in the lesions as well as significantly different fat fractions in normal-appearing VBM (malignant 42% vs. osteoporotic 52%) of both patient groups. CONCLUSIONS: : Although the ADCs of the evaluated malignant and benign VLs showed highly significant differences, the influence of diffusion on the DW-SSFP signal contrast is relatively low compared with other tissue parameters due to the very complex signal mechanism of the SSFP sequence. Thus, the observed DW-SSFP signal contrast of different VLs (hypo-/isointense vs. hyperintense signal) is rather fat- and T2*-weighted than diffusion-weighted. The intermediate diffusion weighting of the applied SSFP sequence, however, helps to shift the different contrasts into a signal range that is easily visually accessible.

Quantitative analysis of vertebral bone marrow perfusion using dynamic contrast-enhanced MRI: initial results in osteoporotic patients with acute vertebral fracture.

PURPOSE: To evaluate the potential of quantitative dynamic contrast-enhanced MRI (DCE-MRI) in vertebral bone marrow (vBM) of patients with acute osteoporotic vertebral compression fractures. MATERIALS AND METHODS: Twenty-six patients with acute osteoporotic fractures (16 female, 10 male, median age 72, range 48-89) and 10 subjects without known history of osteoporosis (6 female, 4 male, median 65, range 31-77) were examined 2D-DCE-MRI. Region of interest (ROI) data in fractured (n = 26) and normal-appearing vertebrae (n = 271) were analyzed with a two-compartment tracer-kinetic-model, providing estimates of at least three independent parameters: plasma flow (PF), plasma volume (PV), and extraction flow (EF). Parameters were correlated with dual x-ray absorptiometry (DXA) (n = 15) and quantitative computed tomography (QCT) densitometry (n = 10). RESULTS: Mean PF was significantly higher in fractures than in normal-appearing vertebrae (69.37 vs. 11.72 mL/100 mL/min). Similarly, mean PV and EF differed significantly. Mean PF was significantly decreased in normal-appearing vBM osteoporotic patients compared to the control group. Mean PF and PV were significantly decreased in lumbar compared to thoracic vertebrae. PV showed a significant correlation with QCT. CONCLUSION: Perfusion parameters were decreased significantly in normal-appearing vBM of patients. Furthermore, significant perfusion alterations were observed in acute osteoporotic vertebral fractures compared to normal-appearing vertebrae.

Surgical therapy of skeletal complications in multiple myeloma.

Patients with multiple myeloma are often treated surgically as though they have bone metastases. Due to major differences in oncological therapy and comparatively long survival times these patients should be considered separately. Seventy-five multiple myeloma patients were treated surgically (83 interventions) for skeletal complications of the disease. Location and dissemination, symptoms, method of surgery, complications, recurrence and survival time were evaluated retrospectively. Most of the lesions were in the axial skeleton or the proximal extremities apart from one distal lesion of the fibula, and most surgery was performed in the spine (35 patients). The mean follow-up of patients was 5.4 years (range 1-25 years). Survival proved to be very favourable (37% at five years). Patients with a single bone lesion, a negative bone marrow biopsy, no paraproteinaemia in serum or a Salmon-Durie-stage I had a better survival probability. Surgical treatment in patients with multiple myeloma was mostly limited to a palliative approach but survival time was better (37% at five years) than in patients with metastatic bone disease which has to be considered in their surgical treatment.

Surgical treatment of bone metastases in patients with lung cancer.

Lung cancer is the leading cause of cancer mortality. Bone metastases are a common complication in lung cancer. The therapeutic approach and the type of surgical treatment of these lesions have not been clearly defined. Outcome and prognosis of patients with bony metastases and a variety of surgical interventions were analysed retrospectively. In 58 patients we performed 62 surgeries. The most common locations of metastases were the spine (32 patients), the proximal femur (10) and the pelvis (11). Twenty-one patients had a singular and 20 had multiple osseous lesions; 17 showed additional visceral involvement. Nine patients had a local progression of their disease and 49 a systemic progression. Patients with local progression (n = 9) had a better prognosis than the patients with systemic progression (p = 0.0083). Fracture (p = 0.0017) worsened prognosis, whereas the number of bone lesions or the presence of a visceral lesion did not. Patients with small lesions showed a better survival than patients with large lesions (p = 0.02). Ten percent of the patients died within 30 days and 78% within one year after surgery. Fracture of bone due to metastatic lung cancer worsens the prognosis whereas the number of bone lesions, the presence of a visceral lesion and the surgical approach do not.

68Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors.

UNLABELLED: We aimed to evaluate (68)Ga-DOTATATE PET/CT for the early prediction of time to progression and clinical outcome after a first cycle of peptide receptor radionuclide treatment (PRRT) in a cohort of patients with well-differentiated neuroendocrine tumors. METHODS: Thirty-three consecutive patients (22 men and 11 women; mean age +/- SD, 57.8 +/- 12.1 y) were investigated at baseline and again 3 mo after initiation of the first cycle of PRRT. (68)Ga-DOTATATE receptor expression was assessed using 2 measures of standardized uptake value (SUV): maximum SUV (SUV(max)) and tumor-to-spleen SUV ratio (SUV(T/S)). Percentage change in SUV scores after PRRT relative to baseline (DeltaSUV) was calculated. After completing 1-3 cycles of PRRT, patients entered the follow-up study, for estimation of time to progression. According to the Response Evaluation Criteria in Solid Tumors, progression was defined on the basis of contrast-enhanced CT. Clinical symptoms, as well as the tumor markers chromogranin A and neuron-specific enolase, were also recorded during regular follow-up visits. RESULTS: The 23 of 31 patients with decreased SUV(T/S) after the first PRRT cycle had longer progression-free survival than did the 8 of 31 patients with stable or increased scores (median survival not reached vs. 6 mo, P = 0.002). For the 18 of 33 patients showing a reduction in SUV(max), there was no significant difference in progression-free survival (median survival not reached vs. 14 mo, P = 0.22). Multivariate regression analysis identified SUV(T/S) as the only independent predictor for tumor progression during follow-up. In the 17 of 33 patients with clinical symptoms before PRRT, DeltaSUV(T/S) correlated with clinical improvement (r = 0.52, P < 0.05), whereas DeltaSUV(max) did not (r = 0.42, P = 0.10). Changes in the tumor markers (chromogranin A and neuron-specific enolase) did not predict DeltaSUV scores, clinical improvement, or time to progression. CONCLUSION: Decreased (68)Ga-DOTATATE uptake in tumors after the first cycle of PRRT predicted time to progression and correlated with an improvement in clinical symptoms among patients with well-differentiated neuroendocrine tumors; DeltaSUV(T/S) was superior to DeltaSUV(max) for prediction of outcome.

Combined diffusion-weighted and dynamic contrast-enhanced imaging of patients with acute osteoporotic vertebral fractures.

OBJECTIVES: To evaluate the potential and to analyze parameter correlations of combined quantitative diffusion-weighted MRI (DWI) and high-temporal-resolution dynamic contrast-enhanced MRI (DCE-MRI) in vertebral bone marrow (vBM) of patients with osteoporosis and acute vertebral compression fractures, providing additional information for a better understanding of the physiological background of parameter changes. MATERIALS AND METHODS: 20 patients with acute osteoporotic fractures were examined with DWI and DCE-MRI at 1.5 T. DCE-MRI was performed with a 2D saturation-recovery turbo-FLASH sequence, acquiring 300 dynamics with a temporal resolution of 1 s. For DWI measurements, a DW HASTE sequence with b-values from 100 to 600 s/mm² was applied. In each patient, ROIs were drawn manually in the fractures and in normal appearing vertebrae. For DCE-MRI, the concentration-time curves of these ROIs were analyzed using a two-compartment tracer-kinetic model in the lesions, providing separate estimates of perfusion and permeability, and a one-compartment model in normal vBM, providing only a mixed representation of perfusion and permeability in terms of a mixed flow parameter K(trans) and the extracellular volume (ECV). In the case of DWI, attenuation curves were fitted to a monoexponential decay model to determine the apparent diffusion coefficient (ADC). RESULTS: Mean perfusion parameters and ADCs were significantly (p<0.001) different in the fractures compared to adjacent normal appearing vertebrae (K(trans): 7.81 mL/100 mL/min vs. 14.61 mL/100 mL/min, ECV: 52.84 mL/100 mL vs. 4.61 mL/100 mL, ADC: 1.71×10⁻³ mm²/s vs. 0.57×10⁻³ mm²/s). ADCs showed a significant correlation with the ECV. CONCLUSION: The quantitative analysis of DWI and DCE-MRI could distinguish osteoporotic fractures from normal appearing vertebrae. A significant correlation found between ECV and ADCs might be able to explain the cause for the increased diffusivity in osteoporotic fractures. Since the other perfusion parameters do not correlate with the ADC, they provide additional pathophysiological information not accessible with DWI.

Measurement of perfusion and permeability from dynamic contrast-enhanced MRI in normal and pathological vertebral bone marrow.

Dynamic contrast-enhanced MRI data in vertebral bone marrow (vBM) are currently analyzed with descriptive indices. The purpose of this study was to develop and evaluate a quantitative approach, considering the tissue composition of vBM. Therefore, a measurement of the water fraction, f(wat), and the precontrast relaxation times, T(10 wat), T(10 fat), was added to the routine protocol. Signal analysis was generalized by allowing for an arbitrary fraction of fat. Plasma flow, plasma volume, extraction flow, and interstitial volume were determined from dynamic contrast-enhanced-MRI data. Simulations were used to determine the sensitivity to the precontrast values and to retrospectively verify the choice of the sequence parameters. Measurements were performed in healthy vertebral bodies (n = 30) and lesions of 15 patients with vertebral fractures. Extraction flow (milliliters per 100 mL/min) provided the strongest normal/abnormal separation: mean (standard deviation) was 0.3 (0.8) in healthy vBM and 6(4) in the fractures. Neglecting the fat component and the approximated signal analysis using relative signal enhancement produced significant differences. We conclude that correcting for the fat component in the signal and parametrization by tracer-kinetic analysis is necessary to avoid misinterpretation and/or systematic errors. The quantitative analysis is equally well suited as a descriptive parameter for the differentiation between normal and abnormal vertebral bone marrow.

The uses and limitations of whole-body magnetic resonance imaging.

BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) is a modern imaging method, free of ionizing radiation, which provides high-resolution display of individual organ systems and of the anatomy of the entire body. METHODS: Selective literature review RESULTS: Multi-channel WB-MRI scanners enable both the high-resolution imaging of the entire body and focused studies of individual organs, through the use of various sequence techniques and contrast modes. The initial application of combined cardiovascular and oncological imaging protocols for the screening of asymptomatic persons has already revealed many cases of cardiovascular disease and of tumors with serious clinical implications. The diagnostic accuracy of M staging with WB-MRI lies in the range of 93% to 97%. WB-MRI provides good contrast of the bone marrow, and has thus been used for the diagnosis of malignant bone marrow disease as well: in particular, it is especially sensitive for multiple myeloma and plays an important role in prognostication and therapeutic decision-making in this disorder. To date, WB-MRI has not been shown to be superior to other diagnostic techniques with respect to hard endpoints, such as prolongation of survival. It also carries the risk of false positive findings. CONCLUSION: Despite these encouraging results, undirected screening by WB-MRI without an appropriate indication, as is currently being practiced in many institutions, is decidedly inadvisable in view of its predicted diagnostic yield below 2% and the lack of evidence for its cost-effectiveness.

Multiparameter MRI assessment of normal-appearing and diseased vertebral bone marrow.

OBJECTIVE: To evaluate spin-lattice (T1) and spin-spin (T2) relaxation times as well as apparent diffusion coefficients (ADCs) of the fat and water components in the vertebral bone marrow (vBM) of patients with benign and malignant lesions. METHODS: Forty-four patients were examined at 1.5 T: there were 24 osteoporotic vertebral fractures (15 women, 9 men; median age: 73, 48-86 years) and 20 malignant vertebral infiltrations (9 women, 11 men; median age: 60, 25-87). Relaxation times were determined separately for the water and the fat component using a saturation-recovery technique for T1 and measurements with variable echo times for T2. ADCs were determined with a diffusion-weighted (DW) echo-planar imaging (EPI) and a single-shot turbo-spin-echo (ssTSE) sequence. RESULTS: T1 of the water component and ADCs were significantly increased in the lesions compared with normal-appearing vBM (malignant: 1,252 vs. 828 ms, osteoporotic: 1,315 vs. 872 ms). ADCs determined with the DW-ssTSE were significantly increased compared with the DW-EPI. ADCs determined with the DW-ssTSE differed significantly between osteoporotic and malignant lesions (1.74 vs 1.35 x 10⁻³ mm²/s. CONCLUSIONS: All parameters exhibit significant differences between normal-appearing vBM and the lesions. However, only the ADCs determined with the DW-ssTSE differed significantly between osteoporotic fractures and malignant lesions, potentially allowing for a differential diagnosis of these two entities.